Drug delivery by inhalation is the preferred route of administration for drugs whose site acting in the lungs. Currently, the metered dose inhaler (MDI) is the most prescribed method of delivering drugs to the lungs. The MDI is the present method of choice because of its high degree of patient acceptance, relative simplicity of use, portability, and multiple-dose capacity. However, the majority of MDIs use chlorofluorcarbons (CFCs) as the system propellant. Due to increasing concerns over the potential adverse effects of CFCs on the atmosphere and the environment, and the international restrictions phasing-out their production over the next several years, alternative systems of aerosolized drug deliver are being developed. MDIs also require a degree of coordination to use. The patient must synchronize inhaling with release of a drug dose. For many patients, this synchronization is difficult to achieve.
Dry powder inhalers (DPI's) deliver a drug powder in an aerosol stream, to be inhaled directly into the lungs without the use of propellants, chlorinated or halogenated. The Spiros.RTM. DPI developed by Dura Pharmaceuticals, Inc., San Diego, Calif., is a multiple-dose, breath-actuated battery-powered, pocket-size delivery system that requires minimal patient coordination. Powder delivery takes place only upon patient inspiratory breathing and is largely independent of inspiratory flow rate, as described in U.S. Pat. Nos. 5,327,883 and 5,577,497, incorporated herein by reference. The Spiros DPI has a molded body with a removable mouthpiece and a disposable multiple-dose drug cassette loaded with 30 individual doses of drug product. The patient's inspiratory flow actives a battery-powered twin-blade impeller, creating a powder aerosol cloud which is inhaled during inspiration. The motor-driven impeller allows the Spiros DPI to operate relatively independent of inspiratory flow rate over the wide range of patient-specific flow rates typically observed in asthmatic children and adults.
Inspiratory flow rate is the air velocity a patient generates when inhaling. In healthy adults during tidal breathing, inspiratory flow rate is about 15 L/min, and with effort, inspiratory flow rates of 100 L/min or more are easily achievable. Inspiratory flow rate in adult patients with moderate to severe obstructive airways disease (mean % FEV.sub.1 of 38.6% predicted) has been demonstrated to average 25.4 L/min (range 13.3 to 50.4 L/min). In normal children and adolescents (3.5 to 15 yrs) breathing through a Turbuhaler.RTM. DPI, only about 1/3 were able to generate an inspiratory flow rate of &gt;60 L/min necessary to create an optimal aerosol from this device.
Perhaps more concerning is the effect of acute wheeze on inspiratory flow rate in asthmatics. It has been demonstrated that 70% of asthmatic children with acute wheeze were only able to generate inspiratory flow rates of &lt;50 L/min breathing through the Rotahaler.RTM. DPI, which was significantly lower than their inspiratory flow rate measured when these children were stable. Since asthma is an obstructive airways disease, it may have a dramatic effect on the ability of adults and children with asthma to create an inspiratory flow rate adequate to operate most DPI's currently available. For example, the Turbuhaler.RTM. DPI (Astra/Draco, Sweden) and the Ventodisk.RTM. DPI (Glaxo, UK) have respirable percentages determined by twin impinger of &lt;8.9% of 15 L/min, which increase to &gt;35% at 60 L/min.
Consequently, while DPI's have several advantages over MDI's, DPI's have not yet found as much widespread acceptance, in part because of their flow rate characteristics, especially as they relate to patients having obstructive or inflammatory lung conditions, such as asthma. The Spiros inhaler, which is now in clinical evaluation, overcomes these well known difficulties associated with DPI's.